Denileukin Diftitox in Treating Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

January 17, 2017 updated by: Wake Forest University Health Sciences

A Phase II Study of ONTAK® (Denileukin Diftitox, DABIL-2) in Patients With Fludarabine-Refractory B-Cell Chronic Lymphocytic Leukemia

RATIONALE: Biological therapies, such as denileukin diftitox, may interfere with the growth of cancer cells and slow the growth of chronic lymphocytic leukemia.

PURPOSE: This phase II trial is studying how well denileukin diftitox works in treating patients with fludarabine-refractory B-cell chronic lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the complete and partial response rate in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia treated with denileukin diftitox.

Secondary

  • Determine the toxicity profile of this drug in these patients.
  • Determine the response rate in patients (regardless of CD25 receptor density) treated with this drug.
  • Determine the progression-free survival and overall survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive denileukin diftitox IV over 1 hour on days 1-5. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response after 8 courses proceed to follow-up. Patients achieving a partial response or stable disease after 8 courses may continue treatment at the discretion of the investigator.

Patients are followed every 3 months for 1 year and then annually until relapse.

PROJECTED ACCRUAL: A total of 12-44 patients will be accrued for this study within 1 year.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • California
      • Orange, California, United States, 92868-3849
        • St. Joseph Hospital Regional Cancer Center - Orange
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Indiana
      • Vincennes, Indiana, United States, 47591
        • Medical Center Vincennes
    • Louisiana
      • Houma, Louisiana, United States, 70360
        • Cancer Care Specialists
      • Shreveport, Louisiana, United States, 71130-3932
        • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Josephine Ford Cancer Center at Henry Ford Health System
    • North Carolina
      • Goldsboro, North Carolina, United States, 27534
        • Southeastern Medical Oncology Center
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Comprehensive Cancer Center at Wake Forest University
    • South Carolina
      • Spartanburg, South Carolina, United States, 29303
        • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Chattanooga Oncology and Hematology Associates
    • Texas
      • Austin, Texas, United States, 78705
        • Southwest Regional Cancer Center - Central

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following criteria at any time during the course of disease (e.g., at initial diagnosis or relapse):

    • Absolute lymphocytosis > 5,000/mm^3
    • Lymphocytes must appear mature with < 55% prolymphocytes
    • More than 30% of all nucleated cells are lymphoid on bone marrow aspirate smear
    • Lymphoid infiltrates compatible with bone marrow involvement by CLL on core bone marrow biopsy
    • Predominant B-cell monoclonal population of cells share the B-cell marker (CD19) with the CD5 antigen in the absence of other pan-T-cell markers by lymphocyte immunophenotyping
  • High-risk disease OR intermediate-risk disease

    • Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least 1 of the following criteria:

      • Massive or progressive splenomegaly and/or adenopathy
      • Weight loss > 10% within the past 6 months
      • Common toxicity grade 2-4 fatigue
      • Fevers > 100.5°F OR night sweats for more than 2 weeks without evidence of infection
      • Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of < 6 months
  • Failed at least 1 prior fludarabine regimen, as defined by 1 of the following criteria:

    • Refractory or intolerant to fludarabine
    • Relapsed within 6 months after completion of fludarabine
  • No CNS leukemia
  • No mantle cell lymphoma in leukemic phase

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • More than 2 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 50,000/mm^3
  • Hemoglobin ≥ 8 g/dL (transfusion allowed)

Hepatic

  • Albumin ≥ 3 g/dL
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • No hepatitis B or C infection

Renal

  • Creatinine ≤ 1.5 mg/dL OR
  • Creatinine clearance ≥ 40 mL/min

Cardiovascular

  • LVEF ≥ 40%

Other

  • No uncontrolled infection
  • No other concurrent serious illness
  • No HIV infection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use two effective methods of contraception (one must be non-hormonal) during and for at least 1 month after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior denileukin diftitox allowed

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • No concurrent corticosteroids as anti-emetics

Radiotherapy

  • No concurrent radiotherapy

Surgery

  • Not specified

Other

  • At least 28 days since prior anticancer therapy and recovered
  • No other concurrent antineoplastic drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Arthur E. Frankel, MD, Wake Forest University Health Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2002

Primary Completion (Actual)

January 1, 2005

Study Completion (Actual)

June 1, 2005

Study Registration Dates

First Submitted

May 14, 2004

First Submitted That Met QC Criteria

May 18, 2004

First Posted (Estimate)

May 19, 2004

Study Record Updates

Last Update Posted (Estimate)

January 19, 2017

Last Update Submitted That Met QC Criteria

January 17, 2017

Last Verified

June 1, 2013

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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